The basic structural unit of most mammalian antibodies is a glycoprotein (MW ~150,000 daltons) comprising four polypeptide chains—two light chains and two heavy chains, which are connected by disulfide bonds (Figure 1). Each light chain has a molecular weight of ~25,000 daltons and is composed of two domains, one variable domain (VL) and one constant domain (CL). There are two types of light chains, lambda (λ) and kappa (κ). In humans, 60% of the light chains are κ, and 40% are λ, whereas in mice, 95% of the light chains are κ and only 5% are λ. A single antibody molecule contains either κ light chains or λ light chains, but never both.

Each heavy chain has a molecular weight of ~50,000 daltons and consists of a constant and variable region. The heavy and light chains contain a number of homologous sections consisting of similar but not identical groups of amino acid sequences. These homologous units consist of about 110 amino acids and are called immunoglobulin domains. The heavy chain contains one variable domain (VH) and either three or four constant domains (CH1, CH2, CH3 and CH4, depending on the antibody class or isotype). The region between the CH1 and CH2 domains is called the hinge region and permits flexibility between the two Fab arms of the Y-shaped antibody molecule, allowing them to open and close to accommodate binding to two antigenic determinants separated by a fixed distance.

The heavy chain also serves to determine the functional activity of the antibody molecule. There are five antibody classes—IgG, IgA, IgM, IgE and IgD—which are distinguished by their heavy chains γ, α, µ, ε and δ, respectively (Table 1). The IgD, IgE and IgG antibody classes are each made up of a single structural unit, whereas IgA antibodies may contain either one or two units and IgM antibodies consist of five disulfide-linked structural units. IgG antibodies are further divided into four subclasses (often referred to as isotypes) although the nomenclature differs slightly depending on the species producing the antibody (Table 1).

Structure/function studies on IgG have been aided by the discovery that the proteolytic enzymes pepsin and papain cleave the molecule into specific fragments with specific biological properties. Treatment of an IgG molecule with pepsin generates the F(ab')2 fragment, which broadly encompasses the two Fab regions linked by the hinge region. Because the F(ab')2 molecule is bivalent, it is capable of precipitating an antigen. Papain cleaves the IgG molecule in the hinge region between the CH1 and CH2 domains to yield two identical Fab fragments, which retain their antigen-binding ability, and one non-antigen–binding fragment—the (Fc) region. The Fc region is glycosylated and has many effector functions (e.g., binding complement, binding to cell receptors on macrophages and monocytes), and serves to distinguish one class of antibody from another.